Primary hyperlipoproteinemia and xanthoma hyperplasia
Introduction
Introduction to primary hyperlipoproteinemia and xanthoma Hyperlipidemia (heperlipidemia) is one or more components and content of plasma lipids exceeding the normal high limit. Because plasma lipids are fat-soluble, they must be combined with proteins to form a water-soluble complex to function throughout the body. The phenotype of hyperemia is hyperlipoproteinemia. Xanthoma is a yellow, orange-yellow or brown-red color formed by the accumulation of lipid-containing tissue cells and macrophages in the dermis tendon. Papules, nodules or plaques, patients often accompanied by systemic lipid metabolism disorders and other systemic abnormalities and a series of clinical symptoms, known as xanthomatosis. basic knowledge The proportion of illness: 0.005% Susceptible people: no special people Mode of infection: contact spread Complications: myocardial infarction diabetes insipidus
Cause
Primary hyperlipoproteinemia and the cause of xanthomas
(1) Causes of the disease
Due to abnormal lipoprotein metabolism, one or several lipoprotein levels in plasma are elevated, except for a few secondary to other systemic diseases, most of which are caused by genetic defects (or interaction with the environment), lipoproteins Metabolism is also affected by age and various hormones in the body. As the age increases, the activity of low-density lipoprotein receptors decreases, the decomposition of low-density lipoprotein decreases, the synthesis of bile decreases, and the synthesis of cholesterol in the liver increases. Estrogen levels are lowered, lipase activity and low-density lipoprotein receptor activity are gradually reduced and hyperlipidemia occurs.
Xanthoma is generally divided into two categories: hyperlipoproteinemia xanthoma and non-hyperlipoproteinemia xanthoma. The etiology of hyperlipoproteinemia can be divided into primary and secondary, primary causes. Unexplained, mostly familial, due to congenital defects in lipid and lipoprotein metabolism, may be related to the degradation of lipoprotein lipase genetic activity or activity affecting lipoprotein breakdown, non-familial is some environmental factors Such as diet nutrition and drugs through a certain mechanism, secondary are seen in atherosclerosis, hypothyroidism, diabetes, mucinous edema, nephrotic syndrome, pancreatitis, hepatobiliary disease, gout and other diseases, also Can be caused by estrogen therapy, alcoholism, obesity, etc., non-hyperlipoproteinemia xanthoma including normal lipoproteinemia xanthomas and other rare congenital lipid metabolism diseases, causing yellow tumors have the following factors:
1 In most cases, plasma lipoprotein increased,
2 abnormal blood vessel wall permeability,
3 serum lipoprotein penetrates the blood vessel wall and deposits connective tissue around the blood vessels.
4 The adventitial cells ingest and process lipoprotein, macrophage aggregation, and after lipoprotein exudation, these cells are transformed into vacuolar foam cells, serum lipoproteins are metabolized in foam cells, and foam cells consistently contain corresponding The lysosomal enzyme structure, the newly occurring xanthomas have a lipoprotein profile that is roughly the same as in the blood, followed by the accumulation of cholesterol esters, cholesterol and phospholipids, and some high-lipoprotein xanthomas are reversible.
According to the characteristics of blood lipids, the World Health Organization classifies primary familial hyperlipoproteinemia into 5 types, the pathogenesis of which is type I: high chylomicronemia, lipoproteinase deficiency; type IIa: high -lipoprotein Blood; type IIb: high-beta lipoproteinemia and high pre-beta-lipoproteinemia, sterol metabolism disorder; type III: wide beta-disease, high pre-beta-lipoproteinemia and high chylomicronemia , lipoprotein metabolism disorder; type IV: high pre-beta-lipoproteinemia, disorders of glucose metabolism, alcoholism, gout; type V: combination of type I and IV, the incidence of different types of hyperlipoproteinemia is also very different, Among them, type II is the most common, and other orders according to the number of cases are IV, III, V, and I. Non-hyperlipoproteinic xanthoma can be caused by abnormal serum proteins or abnormal proliferation of certain cells. Globulinemia, granulocyte and lymphocytic leukemia, histiocytosis and the like.
1. WHO classification is divided into 5 types, of which type II is divided into two subtypes IIa and IIb.
(1) Type I: Hyperlactosis, mainly triglyceride (TG), elevated blood cholesterol can also be normal.
(2) Type II: high cholesterol (TC), which is divided into type IIa and type IIb. The former has a low level of low-density lipoprotein and only elevated cholesterol in blood lipids, but triglyceride is normal, and the latter is low in blood. Both density lipoprotein and very low-density lipoprotein were elevated, and blood lipids were measured as cholesterol and triglyceride was elevated.
(3) Type III: familial abnormal -lipoproteinemia, Apo E-containing lipoproteins such as chylomicrons (CM), very low-density lipoprotein, low-density lipoprotein and receptor-binding disorders due to Apo E gene mutation, These lipid proteins are accumulated in the blood, and blood cholesterol and triacylglycerol can be significantly increased.
(4) Type IV: elevated levels of low-density lipoprotein, which is manifested in a marked increase in blood triglyceride levels, while cholesterol is normal or high.
(5) Type V: The levels of chylomicrons and very low-density lipoprotein in the blood increased, serum triacylglycerol and cholesterol levels also increased, but the increase in triacylglycerol was dominant.
The above classification is more complicated and requires certain experimental conditions, so the clinical simple use of simple typing method, namely: hypercholesterolemia (equivalent to WHO classification IIa), hypertriglyceridemia (equivalent to II, IV type) ) and mixed hyperlipidemia (equivalent to WHO IIb, III, IV, V), the incidence of yellow tumors in hyperlipidemia is not very high, due to atherosclerosis caused by hyperlipidemia It takes a long time to develop, so most patients with hyperlipidemia can have no clinical manifestations and signs, and are only found when physical examination tests for blood lipids (Table 1).
2. Clinical classification
(1) Clinical classification of hyperlipoproteinemia:
1 primary hyperlipidemia: all diseases caused by congenital LP metabolic abnormalities, disease name, morbidity, pathophysiological characteristics, LP receptor, apoprotein (apo) or enzyme deficiency, WHO The phenotype and the type of LP increase (Table 2).
2 secondary hyperlipidemia: the disease caused by abnormal metabolism of acquired LP, the primary phenotype and extent of LP abnormalities are as follows:
A. Hypertriglyceridemia: mild to moderately high TGemia such as diabetes, uremia and/or dialysis patients; mild hypertriglyceridemia such as obesity, estrogen, alcohol or -adrenergic blockers Rare moderate to high levels of hypertriglyceridemia such as systemic lupus erythematosus, abnormal gamma globulinemia, glycogen storage disease type I, and lipodystrophy.
B. Mixed hyperlipidemia: high TG and hyper-chemia exist simultaneously, such as hypothyroidism, nephrotic syndrome, excessive glucocorticoids and diuretics.
C. Hyper-chremia: such as acute intermittent porphyrinuria and anorexia nervosa.
(2) Clinical classification of yellow tumor
1 primary xanthoma: a variety of primary hyperlipoproteinemia, which is family and non-familial, but because the exact pathogenesis of xanthomas is not very clear, it is difficult to explain its specific distribution, rash shape and The link between specific hyperlipidemia.
2 secondary yellow tumor: secondary refers to secondary with some abnormal blood lipids, such as biliary cirrhosis, diabetes, pancreatitis, mucinous edema, nephrotic syndrome, etc., among them, biliary cirrhosis Can develop nodular, flat and palmaroma; diabetes can have flat, rash yellow tumor; pancreatitis can have rash yellow tumor; mucinous edema can have nodular, jaundice; nephrotic syndrome can There are sputum, sputum or rash yellow tumor; abnormal proteinemia such as multiple myeloma, Waldenstrom macroglobulinemia, etc. can be seen in the generalized flat yellow tumor.
3 Yellow tumor without hyperlipidemia: disseminated xanthomas with normal blood lipids occur after the formation of foam cells by the ingestion of lipids by local histiocytosis.
(two) pathogenesis
According to the characteristics of blood lipids, the World Health Organization classifies primary familial hyperlipoproteinemia into 5 types, the pathogenesis of which is type I: high chylomicronemia, lipoproteinase deficiency; type IIa: high -lipoprotein Blood; type IIb: high-beta lipoproteinemia and high pre-beta-lipoproteinemia, sterol metabolism disorder; type III: wide beta-disease, high pre-beta-lipoproteinemia and high chylomicronemia , lipoprotein metabolism disorder; type IV: high pre-beta-lipoproteinemia, disorders of glucose metabolism, alcoholism, gout; type V: combination of type I and IV, the incidence of different types of hyperlipoproteinemia is also very different, Among them, type II is the most common, and other orders according to the number of cases are IV, III, V, and I. Non-hyperlipoproteinic xanthoma can be caused by abnormal serum proteins or abnormal proliferation of certain cells. Globulinemia, granulocyte and lymphocytic leukemia, histiocytosis and the like.
1. The pathogenesis of hyperlipoproteinemia due to abnormal lipoprotein metabolism leads to elevated levels of one or several lipoproteins in plasma, called hyperlipoproteinemia, except for a few secondary to other systemic diseases. Most are caused by genetic defects (or interaction with the environment), called primary hyperlipidemia, clinically common with hypercholesterolemia and hypertriglyceridemia, or a mixture of the two, mainly The reason is related to excessive intake of fat or calories in the diet. Lipoprotein metabolism is also affected by age and various hormones in the body. As the age increases, the activity of low-density lipoprotein receptors decreases, and the decomposition of low-density lipoprotein decreases. Reduced bile synthesis, increased intrahepatic synthetic cholesterol, postmenopausal women due to decreased estrogen levels, lipase activity and low-density lipoprotein receptor activity gradually decreased and hyperlipidemia.
The disease is closely related to lipid metabolism. The main blood lipids in normal plasma are cholesterol, triacylglycerol (triacylglycerol), phospholipids and a small amount of free fatty acids. When the plasma lipid concentration exceeds the normal high limit, it is called hyperlipidemia. When the plasma lipoprotein exceeds the normal high limit, it is called hyperlipoproteinemia. Since most of the lipids are combined with plasma proteins to run the whole body, hyperlipidemia is often reflected in hyperlipoproteinemia, according to ultracentrifugation and electrophoresis. Plasma lipoproteins are divided into 4 categories:
1 high density lipoprotein (HDL), alpha lipoprotein,
2 low density lipoprotein (LDL), beta lipoprotein,
3-polar low-density lipoprotein (VLDL), a pre-beta lipoprotein,
4 chylomicrons (CM), in some pathological cases, intermediate density lipoprotein (IDL), namely broad 8 lipoproteins.
CM mainly contains exogenous triacylglycerol (triacylglycerol). When the content is increased, the appearance of the plasma is turbid. It can be floated into a creamy lid when placed in a refrigerator at 4 °C overnight. VLDL contains endogenous triacylglycerol (triacylglycerol). Accounted for 60%, increased plasma can cause uniform turbidity, but not floating cover, LDL mainly contains endogenous cholesterol, increased content will not cause plasma turbidity, HDL mainly contains protein, followed by cholesterol and phospholipids, normal human plasma lipoprotein Classification and its chemical composition (Table 3), the most important enzyme in lipoprotein metabolism is lipoprotein lipase, insulin is required for synthesis, so the enzyme may be deficient in diabetic patients, and high triglyceride (triacylglycerol) may be caused when the condition is not controlled. ), VLDL and LDL are called atherogenic lipoproteins, and their levels are closely related to coronary heart disease. HDL is an anti-atherosclerotic lipoprotein, HDL in patients with hyperlipoproteinemia. The content is often low.
2. Pathogenesis of xanthoma The range of xanthomas and xanthomatosis is very wide, and its pathogenesis is complex, which can be summarized as follows.
(1) Hyperlipoproteinemia xanthoma: The content of one or more components of plasma lipids in patients with hyperlipoproteinemia exceeds the normal upper limit, and these increased lipids are mainly cholesterol and triacylglycerol (three Acylglycerol) can be deposited in local tissues such as dermis or tendon to form xanthomas. Electron microscopy and radionuclide tracing prove that plasma lipoprotein penetrates into vascular endothelial cells, and lipids in lipoproteins accumulate in cells with xanthomatic damage. There is a positive correlation between the lipids carried by excess lipoprotein in plasma and the abundant lipids in xanthomas.
Hyperlipoproteinemia can be divided into five types according to WHO classification criteria. Type II can still be divided into two subtypes IIa and IIb. The main biochemical characteristics of each type of hyperlipoproteinemia are shown in Table 4.
The causes of hyperlipoproteinemia can be divided into two major categories: primary and secondary. The primary cause is unknown, mostly familial, due to congenital defects in lipid and lipoprotein metabolism, possibly with Lipoprotein lipase has a genetic defect or activity that affects lipoprotein breakdown; non-familial factors are caused by certain environmental factors such as diet, nutrition, and drugs through unknown mechanisms, and secondary diseases are seen in many diseases. Often caused by uncontrolled diabetes, hypothyroidism and mucinous edema, nephrotic syndrome, intrahepatic and extrahepatic bile duct obstruction, pancreatitis, gout, etc., also caused by estrogen therapy, alcoholism, obesity, etc. Therefore, it is also called symptomatic hyperlipoproteinemia, which is caused by systemic diseases leading to excessive lipid transport and metastatic deposition.
(2) Normal lipoproteinemia xanthomas Normal lipoproteinemia xanthomas can be caused by abnormal serum proteins or abnormal proliferation of certain cells.
1 serum protein abnormalities: in some patients with abnormal proteinemia (paraproteinemia) such as multiple myeloma, cryoglobulinemia, macroglobulinemia, hypergammaglobulinemia, lymphoma, leukemia, etc., often blood lipids are normal The local deposition of plasma lipids due to abnormal serum proteins has also been found to detect anti-lipoprotein antibodies in patients with abnormal proteinemia, which may be related to the formation of xanthoma.
2 tissue cell abnormalities: in a group of primary histiocytosis diseases, due to the proliferation of tissue cells with secondary lipid infiltration leading to the formation of xanthomas damage, the patient's blood lipids are often normal, histologically Foam cells are mixed with pleomorphic infiltration of other macrophages, such as juvenile yellow granuloma, systemic rash histiocytoma, fibrosangioma (Fig. 1), and multicentric reticular cell hyperplasia.
3 Langangers Cell Histiocytosis: This is a group of non-inflammatory proliferative diseases including mononuclear macrophages and dendritic cells, formerly known as histiocytosis X, including acute disseminated type (Letterer-Sine disease) ), yellow tumor lesions seen in chronic progressive (Hand-Schüller-Christian disease) and benign localized (bone eosinophilic granuloma).
(3) Congenital lipid metabolism disease: rare cerebral palsy xanthomatosis such as bile acid synthesis deficiency; Tangier disease caused by familial alpha lipoprotein deficiency, intestinal absorption of phytosterol abnormally increased streptocolemia; Some phospholipase-deficient lysosomal lipid storage diseases, such as diffuse body vascular keratomas (Fabry disease), sphingomyelinosis (Niemann-Pick disease), ceramid deficiency disease (Faber fat granulation) Tumor lesions, cerebroside storage disease (Gössie disease) and glycogen storage disease (von Gierke disease) type I and other yellow tumor lesions.
(4) Other factors: such as physical stimulation or trauma, experimental local beatings in rabbits can induce xanthoma damage. Xanthoma is more common in the elbow extension, which has been proven to be associated with repeated stimulation of local tissue cell proliferation, lymphedema Caused by lymphangitis or lymphatic obstruction, the lipoprotein in the lymph fluid accumulates in the extracellular space and is formed by phagocytosis of the tissue cells. Clinically, the xanthoma occurs in the eyelids and there is lymphedema there. Local anatomical factors such as frequent blinking motion stimuli are relevant.
Prevention
Primary hyperlipoproteinemia and prevention of xanthomas
Population prevention
(1) Conducting a wider epidemiological investigation or disease screening: Although the research on the causal relationship between hyperlipidemia and coronary heart disease has gradually become clear, major cities in China, especially Beijing and Shanghai, are targeting various populations. The blood lipids were investigated and the detection rate of hyperlipidemia on behalf of various people in the region was published. The age group of the respondents was as small as the newborn, and the elderly were over 100 years old, but no national high. The investigation report of lipemia is more lacking in the data of the incidence of congenital and hereditary hyperlipidemia in China. The investigation of the latter can make the prevention work start before the birth of the patient and achieve the purpose of prenatal and postnatal care.
(2) Conduct health publicity and education: such as maintaining normal weight; performing physical exercise to ensure appropriate physical activity; and ingesting balanced diet.
(3) Hygienic supervision of susceptible populations: such as regular blood lipid follow-up for older male mental workers or menopausal women.
2. Personal prevention
(1) Primary prevention:
1 Actively accept blood lipids survey and regular health check: especially for middle-aged and elderly men, post-menopausal women, healthy people with hyperlipidemia, coronary heart disease, family history of cerebrovascular disease, various yellow tumor patients, overweight or obese.
2 The above groups should pay attention to self-care: such as actively participating in appropriate physical exercise, avoiding high calorie, high-fat diet, scientific weight loss, etc.
3 active treatment can cause the primary disease of hyperlipidemia: such as diabetes, hypothyroidism and nephrotic syndrome.
(2) Secondary prevention:
1 diet treatment: all patients need to be treated with diet, most patients with mild to moderate hyperlipidemia, after diet treatment, plasma lipoprotein levels can be better controlled, severe hyperlipidemia patients and menstruation Ineffective patients with dietary therapy for a month need to be treated with dietary therapy and medication.
2 Restricting calories: When the calorie intake exceeds the needs of physical activity and basal metabolism, the synthesis and secretion of VLDL in the liver will be stimulated. Therefore, when treating endogenous hyperlipidemia, reduce the total calorie ratio of the diet to change the food. Ingredients are more important. In general, serum VLDL-triacylglycerol (VLDL-TG) levels are positively correlated with obesity, but many obese people have normal blood lipids, while most patients with hypertriglyceridemia have obesity, obesity Hypertriglyceridemia is more common in older children or adult-onset patients. They all have fat cell hypertrophy and relative insulin resistance. After obesity patients lose weight, plasma VLDL decreases significantly and stabilizes at a lower level. In the above, LDL produced by VLDL is also reduced after the production and secretion of VLDL in the liver is reduced. In fact, the level of LDL in the population is slightly positively correlated with the degree of obesity.
3 limit fat intake: due to defects in the body fat decomposition of patients with primary hypercapnia, should strictly limit the intake of saturated fat and excessive unsaturated fat, similarly, patients with mixed hyperlipidemia, have pancreatitis In the case of aura, the fat intake should be immediately limited, and the level of TG (generated by CM) can be rapidly reduced.
Low-fat diets have a significant effect on lowering serum Ch. When saturated fat intake is limited to 8% of total caloric intake, serum Ch levels will decrease by 15% to 20%. The mechanism is not clear, and the recipe is not After replacing saturated fat with saturated fat, LDL-C level is lowered, but it is safe to eat a large amount of unsaturated fat. It is not clear that eating a large amount of unsaturated free fatty acids (FFA) can lower HDL levels, and obese patients increase unsaturated fat. Ingestion can cause cholelithiasis.
4 Limit Ch intake: Ch content in food has an effect on serum Ch level, but each person's response is different. When the normal person limits the dose to below 200mg/d, the plasma Ch level drops by 10% to 15%, excessive intake. Ch can increase the serum Ch, indicating that the feedback inhibition of Ch content in the liver is not ideal. The intake of Ch increases the serum LDL, but some people increase the Ch intake, the serum LDL increases very little, may be Due to the increased storage of Ch in the tissue, excessive intake of Ch can increase HDL-C production. This lipoprotein is a large HDL complex, rich in Ch, and contains apo E, cholesterol-rich VLDL. It also increases, and this VLDL stays in the -band of electrophoresis. The Ch and saturated fat contained in the -band of food increase the serum Ch, and there is no interdependence between them. The reduction of saturated fat in food can reduce the production of VLDL, serum The TG level has dropped.
5 The role of carbohydrates: The effect of eating carbohydrate foods on lipid metabolism is very different in normal people. After ingesting high-carbohydrate foods, serum TG levels decrease for about 10 hours. If you continue to consume this food, then High TGemia will occur within 48 to 72 hours, serum TG peaks within 1 to 5 weeks, and those with high basal TG levels and those with excessive calorie intake are more active, but if they continue to ingest High-carbohydrate foods for 1 to 8 months, most people's serum TG will drop to the basal level, only a few people still have persistent high TG, and patients with endogenous and mixed hyperlipidemia have similar reactions. Therefore, any hyperlipidemia is not particularly sensitive to carbohydrate reactions. Only patients with endogenous and mixed hyperlipidemia are extremely sensitive to excessive caloric intake. High carbohydrate intake can make serum HDL. Increased, but the increase is small.
6About alcohol intake: Alcohol stimulates the synthesis of VLDL in the liver. Therefore, serum TG is elevated after drinking. Some patients with endogenous hypertriglyceridemia have a particularly high TG after drinking. After cessation, the TG level can return to normal. Long-term drinking can increase cholesterol synthesis, and the rate of conversion to bile acid is slowed down, so serum cholesterol is elevated. According to the population survey, the level of HDL-C can be increased in drinking about 60ml per day, but not everyone has this. Kind of reaction.
7 Other foods: The effect of fiber food on plasma lipids is not clear. The effects of calcium, magnesium, trace elements and vitamins E, C and B are also uncertain. Coffee and sucrose have little effect on serum lipid levels.
8 standard recipes: diet adjustment, is very important for the treatment of various high-lipoproteinemia, some patients can play a therapeutic role only by diet adjustment, although various types of patients have their own characteristics, but the standard diet can be Applicable to a variety of patients with hyperlipoproteinemia, the main requirements of the standard recipe are as follows:
1 can reduce weight to the desired level and maintain at this level.
2 reduce fat intake, saturated fat intake should be less than 8% of total calorie intake.
3Ch intake <250mg / d.
4 In addition to the necessary protein intake and the above fat intake, supplement the remaining calories with carbohydrates.
5 people with high TG should be prohibited from drinking alcohol.
Those with elevated serum VLDL and IDL need to limit calories and lose weight. Adult weight loss treatment is to control the calorie intake at 3.5-5.0 MJ/d (800-1200 kcal/d).
The weight of patients with familial hyper-chremia is mostly in the normal range. If the patient is obese, the blood Ch may decrease slightly after losing weight, but the effect of different patients is not the same. Anyone with hyper-Chemia should take low Ch. And low-saturated fat diet, but can only reduce serum Ch by about 10%, and the higher the serum Ch level, the worse the effect, all patients with hyperlipidemia, should adhere to the standard diet after weight loss, primary Patients with hypercapnia (LPL deficiency or cofactor apo-C-II deficiency) should limit fat to 10-20 g/d, at least 5 g of which is vegetable oil, such as safflower oil rich in essential fatty acids, while limiting fat Should be supplemented with vitamins.
Many of the hyperlipidemias are caused by improper diet or secondary to diabetes, hypothyroidism and other diseases, which can be prevented if they are taken early.
A. Dietary therapy: Controlled diet is the basic measure for the treatment of this disease. For patients with high chylomicronemia (I, V), generally only low-fat diet is required; V-type must also limit carbohydrates and cholesterol, and give high Protein to ensure nutrition; for endogenous high triglyceride (triacylglycerol) patients (III, IV, V), mainly to limit total calories and sugar; for hypercholesterolemia (IIa, IIb), Low cholesterol, low saturated fatty acid diet should be used, and unsaturated fatty acids such as linoleic acid should be added.
B. Drug treatment: diet therapy can not be controlled, must be treated with lipid-lowering drugs, including enhanced VLDL clearance, mainly to reduce the clofibrate of triacylglycerol (triacylglycerol) and its derivatives; strengthen LDL decomposition, mainly lower cholesterol Cholestyramine (cholestyramine) and lipid-lowering resin No. 2, No. 3; mainly inhibits the synthesis of VLDL and LDL, and simultaneously reduces the niacin of triacylglycerol (triacylglycerol) and cholesterol. Many new lipid-lowering drugs such as fenofibrate, as well as some Chinese medicines that can lower blood lipids such as Alisma, Polygonum cuspidatum, Milk Thistle, Shouwu, Hawthorn, Tea Tree, Mulberry, Mao Dongqing, Cassia, etc. Bucao (Probucol), 0.5g, 2 times / d, morning and evening after meals, for 6 weeks to 2 years, is effective for both jaundice and jaundice with or without hypercholesterolemia.
C. Local treatment: localized damage such as jaundice and jaundice, etc., if it affects beauty or function, it is mainly treated with local treatment, such as trichloroacetic acid spotting, liquid nitrogen freezing therapy, carbon dioxide laser or surgical resection, etc. .
Complication
Primary hyperlipoproteinemia and complications of xanthoma Complications, myocardial infarction, diabetes insipidus
Familial hyperphosphate
Male heterozygous patients with arteriosclerosis can be complicated by myocardial infarction, LPL deficiency or apo CII deficiency may be associated with hepatosplenomegaly, familial hypertriglyceremia may be complicated by pancreatitis; lipemia-retina (ocular fundus) The color is ketchup).
2. Severe hyperlipoproteinemia type II
Often with coronary artery disease and other cardiovascular diseases or secondary hyperlipoproteinemia.
3. Eruptive xanthoma
Almost without exception, it occurs in high chylomicronemia, ie, hyperlipoproteinemia type I and type V, as well as type III or secondary hyperlipoproteinemia.
4. Disseminated xanthomatosis
About one-third of patients have temporary or mild diabetes insipidus due to damage to the hypothalamic-neuronal pituitary.
Symptom
Primary hyperlipoproteinemia and symptoms of xanthoma hyperplasia Common symptoms Abdominal pain Hepatosplenomegaly Angiogenesis dyslipidemia Abnormal jaundice Atherosclerotic nodules Weight loss Parotid swelling Chest pain
1. Identification of various types of hyperlipidemia
(1) Congenital hyperlipidemia:
1 familial hyper-chremia:
A. The early appearance of CHD in young men and the high-crevity found in this disease are the main clinical findings of the disease. Male heterozygous patients with arteriosclerosis, the age at which the first myocardial infarction occurred was 41 years old, female patients If there is no additional risk factor, there may be no atherosclerosis in life, and there is no similar increase in the incidence of peripheral vascular disease and cerebrovascular disease.
B. Tendon xanthomas, the lipid deposited on the tendon, is the most diagnostic sign for the disease. It usually has irregular nodules in the bilateral Achilles tendon and the extensor tendon of the hand, but may develop. For the diffuseness of the tendon, the general thickening.
2 abnormal -LP:
A. The disease can be found in early years of arteriosclerosis, flat or nodular xanthoma patients and hyperlipidemia patients found in routine physical examination.
B. Male hyperlipidemia occurs after 30 to 40 years of age, and women appear after menopause.
The abnormality of C.apo E can be measured at birth.
D. The yellow tumor appears later, mainly in the palmatum, which is distributed in the palm print, nodular or nodular rash yellow tumor.
E. The clinical manifestations of male arteriosclerosis appear around 50 years old. Peripheral vascular lesions are common and the incidence of CHD is also increased. Peri-menopausal peripheral vascular lesions and CHD are faster than non-clinical patients.
3LPL defects or apo CII defects:
A. Insufficient fat is infancy, and as children grow, they gradually learn to avoid high-fat diets (such as whole-fat dairy products).
B. Abdominal pain (often accompanied by pancreatitis) occurs in high CM, TG.
C. Eruptive xanthomas are distributed on the surface of the extensor muscles, such as the elbow, knee and hip, which are diagnostic for chronic hypercapnia, and the rash yellow tumor disappears after the CM level drops to normal.
D. Hepatosplenomegaly, but the latter is rare, due to the accumulation of lipid-filled foam cells in the liver and spleen, such as the fat-free diet, the liver and spleen shrink rapidly.
4 familial hypertriglyceridemia: clinical manifestations: the vast majority of no clinical findings, mostly due to physical examination, occasionally due to the onset of high TG-related disease, its susceptibility to CHD, obesity and diabetes The rate is the same as that of the normal population. The yellow tumor is not specific, such as plasma TG 22.58 mmol / L (2000 mg / dl), followed by significant CMemia and a group of signs and symptoms associated with it called CM Chylomicronemia syndrome (CMS), manifested as: abdominal pain and/or pancreatitis, even chest pain, near memory loss, peripheral sensory abnormalities similar to carpal tunnel syndrome (capaltunnel syndrome), lipemia-lipemia- Retina fundus vascular color is ketchup color, liver large (common), splenomegaly (rare) and rash yellow tumor, such as blood TG <22.58mmol / L (2000mg / dl), the above performance is eliminated.
5 Familial mixed hyperlipidemia: clinical manifestations: males showed CHD in early years, and the average age of myocardial infarction was 40 years old. Smoking played a significant role in promoting "clinical heart disease". Obesity and obesity in patients with this disease Hypertension is more common, generally no yellow tumor, even non-specific jaundice can be seen.
(2) Identification and mechanism of secondary hyperlipidemia:
1 high TGemia:
A. Diabetes: a. Untreated insulin-dependent diabetes mellitus and untreated patients with non-insulin-dependent diabetes mellitus, with low LPL activity in adipose tissue and muscle, resulting in mild to moderate increases in plasma TG levels and HDL- c level drops, b. In the case of insulin resistance and mild insulin deficiency, hypertriglyceridemia is due to the adipose tissue mobilizes a large number of free fatty acids (FFA), re-esterified by the liver, as endogenous VLDL Caused by secretion.
B. Chronic uremia and dialysis: Many patients with chronic uremia have elevated plasma VLDL, TG levels, decreased HDL-C levels, and persisted until maintenance hemodialysis and peritoneal dialysis, and the above-mentioned LP abnormalities appear to be associated with LPL-mediated TG clearance. The defects are related to dialysis patients with significant arteriosclerosis, smoking, and other factors such as hypertension.
C. Others: a. Obesity, the increase in TG levels caused by estrogen and alcohol consumption is extremely mild, usually does not reach the "abnormal" level, may be due to a slight increase in liver secretion VLDL, b. diuretics and - Adrenergic blockers can increase the level of TG slightly. The mechanism may be that the former increases LDL level, the latter lowers HDL level, c. Moderate to high hypertriglyceridemia is extremely rare and can occur in the system. Patients with lupus erythematosus and abnormal globulinemia are the result of interaction between immunoglobulin and LP. d. Moderately high TGemia is also only found in rare diseases such as glycogen accumulation disease type I, fat nutrition. Bad and so on.
2 mixed hyperlipidemia
A. Hypothyroidism: The normal progress of most steps in LP metabolism requires the participation of thyroid hormones, especially LDL receptor maintenance requires thyroxine, thyroid dysfunction due to catabolic defects, resulting in elevated LDL levels; VLDL debris The damage of the function is cleared, resulting in accumulation of CM; finally, due to the low level of LPL, high TG is caused.
B. Nephrotic syndrome: With the loss of albumin in the urine and the appearance of hypoalbuminemia, the levels of VLDL or LDL or both are increased, the abnormalities of the above LPs are associated with increased liver lipid synthesis and TG-deficient LP catabolism defects. Correlation, the latter defect is caused by the loss of related factors that maintain LPL function in the urine.
C. Excessive glucocorticoids: High levels of glucocorticoids are seen in Cushing's syndrome and exogenous steroid therapy, often accompanied by increased levels of VLDL and/or LDL.
3 Hyper-Hemia: Increased LDL levels are occasionally seen in people with high-saturated fatty acids and high-Ch diets, and the mechanism of most hyper-chremia in the population is still difficult to explain, because it is thought that under the influence of environmental factors, The role of disease, so called "multiple genetic factors" disease, acute intermittent hematoporphyria and acute anorexia patients with plasma LDL levels can also be elevated.
2. The identification of various types of xanthoma is distinguished according to the morphology, location, number and related properties of xanthoma. There are mainly the following types in clinical practice:
(1) flat xanthomas: more common, damage from needle to egg, yellowish to brownish yellow, flat soft patches or slightly raised plaques, occur in the eyelids, neck, torso, elbow, armpits, The armpits, the medial side of the thigh, the buttocks and the palms have the following subtypes and are characteristic of certain diseases:
1 xanthoma: is one of the most common xanthoma, especially seen in the proximal iliac crest, single or multiple, slow development, can spread on both sides, lower eyelids, and even form a yellow circle around the periorbital Very special, more common in middle-aged women, there are statistics 25% of patients with xanthoma with hyperlipoproteinemia type II, showing elevated plasma cholesterol, especially in young people, but after 40 years old There are often no lipid abnormalities. Recently, some patients with non-hyperlipidemia xanthomas have been reported to have a small amount of lipoprotein deficiency, and some patients have an increased risk of hardening of the arteries.
2 palm-striped xanthoma: is a kind of line-like flat xanthoma lesions distributed along the palmprint and palm palm surface texture, often very fine, easily overlooked, often a special symptom of type III hyperlipoproteinemia, abnormal performance Increased beta-lipoprotein, may also be associated with secondary hyperlipoproteinemia due to obstruction of the intrahepatic and extrahepatic bile ducts,
3 generalized flat xanthomas: rare, flat orange or brownish yellow spots and plaques, symmetrical around the facial eyelids, both sides of the neck, upper torso and upper arm, generally seen in the elderly, the prognosis is good, but about Half of patients may be associated with various abnormal proteinemias, such as multiple myeloma, macroglobulinemia, lymphoma or leukemia. Xanthoma often occurs several years before these diseases, so patients should be carefully examined. Hyperlipoproteinemia may or may not be, such as no hyperlipidemia, it is called generalized normal lipemia flat yellow tumor.
(2) Nodular xanthomas: early soft papules or nodules, orange to brownish yellow, can be fused or enlarged to a plaque of 2 to 3 cm in diameter. We have seen a single lesion with a diameter of 8 cm. Nodular xanthomas, the damage develops slowly, is not easy to subside, becomes solid with the increase of fibrosis, the surface is hemispherical or lobable, pedicled, and occurs on the extension side, such as elbow, knee, knuckle extension, Hips, etc., single or in groups, patients often with hyperlipoproteinemia type II or III, manifested as an increase in plasma cholesterol and (or) triglyceride (triacylglycerol), can be found atherosclerotic vascular disease Such as angina pectoris, myocardial infarction and peripheral vascular insufficiency, may also be associated with hypothyroidism or biliary cirrhosis caused by secondary hyperlipoproteinemia, and xanthomas associated with nodular xanthoma often Xanthoma, in essence, is a nodular xanthoma that occurs in a special part of the tendon, ligament and fascia. The nodule is deep, smooth, firm, and of varying sizes. The surface skin can move as usual, most commonly in Achilles tendon and knee, elbow and back of the hand tendon, can also be accompanied , humeral trochanter and elbow periosteal xanthoma, jaundice almost always indicates a potential systemic disease, such as severe hyperlipoproteinemia type II, often with coronary artery disease and other cardiovascular diseases or secondary Hyperlipoproteinemia.
Type IV: also known as familial high triglyceride (triacylglycerol), familial combined with hyperlipoproteinemia, often after 20 years of age, mostly flat, nodular xanthomas, may be accompanied by rapid progress Atherosclerosis and recurrent pancreatitis, increased blood uric acid and abnormal glucose tolerance.
3. Clinical points
(1) yellow tumor: a localized skin protuberance, yellow, orange, mostly nodular, maculopapular, papular, soft texture, mainly due to the accumulation of lipid-phagocytic macrophages in the skin ( Caused by foam cells, yellow tumors occur in the Achilles tendon, the tendon of the hand or the back of the foot, the knee, the rectus femoris, the shoulder deltoid muscle tendon, the junction of the humerus and the quadriceps, the triceps triceps At the junction of tendon, palm wrinkles, around the eyelids and the skin of the trunk and limbs, oral mucosa, after effective lipid-lowering treatment, most of the yellow tumor can gradually disappear.
(2)
(3)
(4)
(5)
(6)(IGT)2IGT
(7)
Examine
()(HDL)2
1.
12h>6.0mmol/L(240mg/dl);>2.3mmol/L(200mg/dl);>4.0mmol/L[=-(HDL+)(mmol/L)];>0.9mmol/L
2.
>600mmol/L
3.
CrT3T4
()(Touton)
Diagnosis
diagnosis
1.
(1)
ChCh7.7512.93mmol/L(300500mg/dl)TG;LDL;Ch;
-LP;ChTG;VLDL(cholesterol esterCE)VLDL;apo E;LDLHDL
LPLapo CLPLLPLApo C(radio immunoassayRIA)LPLPL
(2)TG20;TGVLDLTG(-)
(3)
CMTG
apo B
VLDLLDL
HDLHDL-(HDL-C)apo A
Differential diagnosis
